Identifying Risk Factors for Reduced Vancomycin Susceptibility in Clostridioides difficile Infections

Taryn A. Eubank, PharmD, BCIDP

Image credits: University of Houston

The association between reduced vancomycin (VAN) susceptibility in clinical Clostridioides difficile isolates and poor clinical outcomes is well established. Although, specific factors contributing to infections with these strains remain unclear. This study identified certain ribotypes (RTs), notably RT 027, as significant independent risk factors for reduced VAN susceptibility.¹

Multivariable analysis indicated that RT 027 was significantly associated with reduced VAN susceptibility, with an odds ratio (OR) of 13.4 (95% confidence interval (CI): 7.7–23.4; p < 0.0001). Ribotype 255 also showed a positive correlation (OR: 2.9; 95% CI: 1.4–6.1; p = 0.005), while ribotype 014-020 was more likely to be susceptible (OR: 0.41; 95% CI: 0.21–0.80; p = 0.0092). Notably, no specific patient or hospitalization factors predicted infections with reduced susceptibility strains.

In an exclusive conversation with Contagion, Taryn A. Eubank, PharmD, BCIDP, research assistant professor at the University of Houston College of Pharmacy, elaborated on these findings, “This highlights to me that diagnostic testing that includes identification of RT 027 could greatly guide clinical practice.”

From 2016 to 2021, 594 hospitalized patients with C difficile infection (CDI) were analyzed. 173 (29%) patients showed reduced susceptibility to VAN, with a minimum inhibitory concentration (MIC) of 2 µg/mL for MIC50 and 4 µg/mL for MIC90. Demographics included 57% female, 55% over 65 years old, and 59% white/non-Hispanic; additionally, 53% experienced non-severe CDI episodes.¹

Eubank elaborated on the multivariable analysis designed to identify risk factors for reduced VAN susceptibility, particularly concerning RTs, “A forward, stepwise, multivariable logistic regression modeling was performed to analyze independent risk factors of reduced VAN susceptibility. Variables from univariate analysis includes patient demographics and disease characteristics) with p<0.2 were included in the multivariable model. Inclusion of variables with p<0.2 into the model was to address confounding and truly get independent risk factors. All variables with a p<0.05 from the multivariable logistic regression were considered statistically significant.”

Clinical isolates of C diff were subjected to agar dilution testing for VAN susceptibility and ribotyping. Reduced susceptibility was defined as a MIC exceeding 2 µg/mL. A review of medical records focused on host, pathogen, and hospital characteristics to evaluate predictors of reduced VAN susceptibility.¹

Eubank concluded the conversation by discussing the implications of these findings for clinical practice in managing CDI, particularly in relation to surveillance and antibiotic prescribing, “Due to susceptibility testing of C difficile not being feasible in clinical practice because of difficulty and time constraints, we really wanted to complete this analysis as a follow up to PMID 38382090 to help guide clinicians at the bedside. Interestingly, essentially all patient demographics and disease characteristics did not independently predict VAN-reduced susceptibility aside from strain type. While identifying every strain in clinical practice may not be feasible or cost effective, screening specifically for RT 027 may be warranted. This could help clinicians stratify fidaxomicin versus vancomycin use since patients treated with VAN that are infected with a reduced susceptible strain have been shown to have a reduced sustained clinical response, and specifically treatment failure with continued symptoms at end of therapy. (see figure 1 – PMID 38382090).”

Figure 1 – PMID 38382090

Image Credits: Taryn A. Eubank, PharmD, BCIDP

Previous coverage from Contagion indicated that reduced VAN susceptibility is linked to poorer treatment outcomes, including lower rates of sustained clinical response (SCR) and initial cure. Approximately 34% of isolates exhibited diminished susceptibility, with RT 027 being the most prevalent (77.4%).²

The study, conducted from 2016 to 2021, analyzed 300 adults diagnosed with CDI who received oral vancomycin. Patients with reduced susceptibility had a 76% SCR rate compared to 86% for susceptible strains (P = .031). Initial cure rates were also lower for these patients, with 89% achieving a cure versus 96% for those with susceptible strains (P = .04). Reduced susceptibility was an independent predictor of 30-day SCR (OR: .52; 95% CI: .28–.97; P = .04).²

Both studies highlight the relationship between reduced VAN susceptibility in C diff isolates and poor clinical outcomes. The first study identifies RT 027 as a significant risk factor, while the second confirms that diminished susceptibility is linked to lower rates of sustained clinical response and initial cure.

With the rising prevalence of these strains, particularly RT 027, there is an urgent need for improved clinical monitoring and susceptibility testing. Together, these findings underscore the importance of understanding C diff epidemiology to guide effective treatment strategies and address antimicrobial resistance in this persistent public health challenge.

References

1. Eubank T, Dureja C, Gonzales-Luna A, et. al. Reduced vancomycin susceptibility in Clostridioides difficile is associated with specific ribotypes, Open Forum Infectious Diseases, 2024;, ofae588, https://doi.org/10.1093/ofid/ofae588

2. Eubank T, Dureja C, Garey K, et. al. Reduced Vancomycin Susceptibility in Clostridioides difficile Is Associated With Lower Rates of Initial Cure and Sustained Clinical Response. Clinical Infectious Diseases. Published February 21, 2024. Accessed October 30, 2024. Doi: https://doi.org/10.1093/cid/ciae087